Aldosterone is important in sodium and potassium homeostasis in normal and hypertensive subjects. We have identified three areas where significant unanswered questions can be at least partially resolved by experimental methods available to use. 1. There is now both indirect and direct evidence for the presence of glycoprotein in the urine of normal and hypertensive subjects which stimulates aldosterone production. We have developed an in-vitro isolated adrenal glomerulosa cell assay in order to test these fractions. Preliminary studies are now underway using a con A glycoprotein eluates and comparing the effect of this material against samples obtained in the laboratories of other investigators to confirm the presence of this material. Preliminary studies of the effect of acidosis upon aldosterone with this system have shown two different types of response to that stimulus depending upon the media used for incubation. 2. We have shown that the uptake of 14C riboflavin into flavin adenine dinucleotide (FAD) is blocked by two riboflavin antagonists. Prior treatment of rats with these antagonists blocks the aldosterone induced antinatriuresis but not kaliuresis as seen in control rats. These studies indicate that flavokinase plays an important intermediary role in adlosterone action. 3. We have examined the mineralocorticoid receptor antagonism of progesterone and several other progestins against DOC in the rat. Progesterone in large doses was able to block the DOC effects both in-vivo and in-vitro. We are now preparing multiple hormone measurements and will use these profiles to reproduce these effects in animal models.